Evaluation of dose-dependent effects of dapagliflozin on urinary glucose and plasma ketone bodies in healthy dogs.

OBJECTIVE

To evaluate the dose-dependent effects of single dosing of dapagliflozin on pharmacodynamics, diuresis, and ketogenesis in dogs.

METHODS

This study included 5 healthy Beagles. A single dose of dapagliflozin (0.1, 0.3, or 1.0 mg/kg) or placebo was orally administered (randomized 14-day intervals) to each dog. Blood and urine samples were collected prior to administration and at 1, 2, 3, 4, 5, 6, 9, 12, and 24 hours after administration. A urinary catheter was placed from 0 to 6 hours after administration to monitor urine volume and collect samples; thereafter, urine was collected using a metabolic cage. Plasma ketone bodies, sodium, potassium, chloride, and glucose concentrations were measured. Urinary sodium, potassium, chloride, glucose, and urine volume were measured and compared among the treatment groups.

RESULTS

24-hour urinary glucose excretion was significantly increased in the 0.3-mg/kg group compared with the 0.1-mg/kg group. However, no significant difference in 24-hour urinary glucose excretion was observed between the 0.3-and 1.0-mg/kg groups. Plasma ketone body concentration was significantly higher in the 1.0-mg/kg group compared with the placebo group at 4, 5, 6, 12, and 24 hours after administration. The 6-hour urine volume (mL/kg) was significantly higher in the 1.0-mg/kg group compared with the placebo group.

CONCLUSIONS

In healthy dogs, a single oral administration of dapagliflozin at 1.0 mg/kg induced both ketogenic and diuretic effects.

CLINICAL RELEVANCE: This study provides preliminary insight into dapagliflozin's effects in healthy dogs; further studies are needed to assess relevance in dogs with heart failure.